Method and System for Providing Continuous Calibration of Implantable Analyte Sensors

ABSTRACT

Methods and systems for providing continuous monitoring of analytes using analyte sensors are disclosed. Techniques include a receiving device comprising a communication unit configured to wirelessly communicate with a first and second transmitter unit, processors coupled to the communication unit and a memory coupled to the processors storing instructions which, when executed by the processors receive one or more first data signals from the first transmitter unit; receive, while the first glucose sensor is positioned and the second glucose sensor is positioned, a user input corresponding to a code; receive one or more second data signals from the second transmitter unit, wherein the communication unit is configured to wirelessly communicate with the second transmitter unit after termination of wireless communication with the first transmitter unit; process the second data signals to produce processed data signals; and provide the processed data signals for display.

RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 16/181,075, filed Nov. 5, 2018, which is a continuation of U.S.patent application Ser. No. 14/850,957 filed Sep. 11, 2015, now U.S.Pat. No. 10,117,614, which is a continuation of U.S. patent applicationSer. No. 13/959,302 filed Aug. 5, 2013, which is a continuation of U.S.patent application Ser. No. 13/022,620 filed Feb. 7, 2011, now U.S. Pat.No. 8,506,482, which is a continuation of U.S. patent application Ser.No. 11/365,340 filed Feb. 28, 2006, now U.S. Pat. No. 7,885,698,entitled “Method and System for Providing Continuous Calibration ofImplantable Analyte Sensors”, the disclosure of which is incorporatedherein by reference for all purposes.

BACKGROUND

Continuous monitoring of analytes of a patient generally uses an analytesensor that that is at least partially implanted in the patient so as tobe in fluid contact with the patient's analytes such as interstitialfluid or blood. The analyte sensor typically is replaced after apredetermined time period such as three, five or seven day period, whena new sensor is implanted in the patient to replace the old sensor.During the sensor replacement process, a gap or interruption in theanalyte monitoring occurs. For example, during the time period in whichthe patient removes the implanted analyte sensor to replace with a newanalyte sensor, the patient is unable to monitor or determine theanalyte values such as glucose levels. In this manner, with continuousglucose monitoring systems presently available which use short termanalyte sensors, there is always a gap in service during which dataassociated with the measurement of the patient's analyte levels cannotbe obtained.

In addition, calibration of each implanted analyte sensor, which isnecessary before data from the analyte sensor can be obtained, islaborious, time consuming, and error prone. Factory calibration is not apractical approach due to substantial sensor to sensor variability ofsignal strength introduced during the manufacturing process, and also,due to additional variability imposed by the sensors' response to thein-vivo environment which varies from patient to patient.

Thus, typically it is necessary to perform in-vivo calibration, in whichthe analyte sensor is calibrated, post implantation, by comparison witha reference blood glucose value. Generally these reference blood glucosevalues include capillary blood glucose values obtained by finger or armstick using a conventional blood glucose meter. To perform thecalibration using the reference blood glucose values, a substantialnumber of capillary values such as, for example, one to four capillarymeasurements daily, are necessary to ensure the continued calibration(and thus, accurate) values determined by the analyte sensors.

Moreover, calibrations may sometimes be inaccurate due to transientsensitivity changes which generally occur early in the lifetime of animplanted sensor, and sometimes referred to as early sensitivityattenuation, or ESA. If a calibration is assigned to an analyte sensorundergoing a transient change in sensitivity, inaccurate sensor readingsor measurements will result at a later point in time, when thesensitivity reverts to its “true” value.

Further, the typical calibration process is performed for each newlyimplanted glucose sensor. More specifically, with the placement of eachglucose sensor, a new set of blood capillary reference values areobtained, and which is the sole basis (or reference) for calibration ofthat particular sensor during the usage life of the sensor, for example,during a three, five or a seven day period.

In view of the foregoing, it would be desirable to have an approach toprovide methods and system for continuous analyte monitoring where nogap in service can be achieved. In addition, it would be desirable tohave methods and a system to verify the stability of a newly implantedsensor, before obtaining user-accessible analyte data from the sensor.Furthermore, it would be desirable to have methods and system forcontinuous analyte monitoring for continuous calibration of analytesensors and which minimizes the number of necessary fingerstick (orarmstick) calibrations of the analyte sensors using glucose meters, andalso, to provide alternate reference.

SUMMARY OF THE INVENTION

In view of the foregoing, in accordance with the various embodiments ofthe present invention, there is provided a method and system in whichshort term sensors may be calibrated based on the data associated withprior short term sensors by providing an overlap in the sensor placementduring the sensor replacement process such that fewer, or in the limit,no additional capillary blood glucose values are needed for calibrationof subsequent sensors, and further, analyte levels are continuouslymonitored without any interruption, for example, during the periodicsensor replacements in the continuous analyte monitoring system.

These and other objects, features and advantages of the presentinvention will become more fully apparent from the following detaileddescription of the embodiments, the appended claims and the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram illustrating a continuous analyte monitoringsystem for practicing one embodiment of the present invention;

FIG. 2 is a flowchart illustrating the continuous calibration of analytesensors in the continuous analyte monitoring system in accordance withone embodiment of the present invention;

FIG. 3 is a flowchart illustrating correlation and calibration steps230, 240 of the continuous calibration of analyte sensors in thecontinuous analyte monitoring system shown in FIG. 2 in accordance withone embodiment of the present invention;

FIG. 4 is a chart illustrating the timing of the continuous calibrationof analyte sensors in the continuous analyte monitoring system inaccordance with one embodiment of the present invention;

FIG. 5 is a chart illustrating the measured analyte values of a firstcalibrated analyte sensor in the continuous analyte monitoring system inaccordance with one embodiment of the present invention;

FIG. 6 is a chart illustrating the measured analyte values of a secondanalyte sensor which is implanted while the calibrated first analytesensor is implanted in the continuous analyte monitoring system inaccordance with one embodiment of the present invention;

FIG. 7 is a chart illustrating the measured analyte values of the secondanalyte sensor which is calibrated and correlated with the measuredvalues from the calibrated analyte sensor in accordance with oneembodiment of the present invention; and

FIG. 8 is a chart illustrating measured analyte values after the removalof the first analyte sensor, and from the calibrated second analytesensor in accordance with one embodiment of the present invention.

DETAILED DESCRIPTION

FIG. 1 is a block diagram illustrating a continuous analyte monitoringsystem for practicing one embodiment of the present invention. Referringto FIG. 1, a continuous analyte monitoring system 100 includes analytesensor 111A operatively coupled to a transmitter unit 121A, and analytesensor 111B operatively coupled to transmitter unit 121B. Further shownis a receiver/data receiving unit 130 which is operatively coupled totransmitter unit 121A and transmitter unit 121B. The receiver/dataprocessing unit 130 in one embodiment is configured to communicate witha remote terminal 140 and a delivery unit 150. The remote terminal 140in one embodiment may include for example, a desktop computer terminal,a data communication enabled kiosk, a laptop computer, a handheldcomputing device such as a personal digital assistant (PDAs), or a datacommunication enabled mobile telephone. Moreover, the delivery unit 150may include in one embodiment, but not limited to, an external infusiondevice such as an external insulin infusion pump, an implantable pump, apen-type insulin injector device, a patch pump, an inhalable infusiondevice for nasal insulin delivery, or any other type of suitabledelivery system.

Referring to FIG. 1, the receiver/data receiving unit 130 is configuredto receive analyte related data from transmitter unit 121A andtransmitter unit 121B over a wireless data communication link such as,but not limited to, radio frequency (RF) communication link, Bluetooth®communication link, infrared communication link, or any other type ofsuitable wireless communication connection between two or moreelectronic devices which may further be uni-directional (e.g., fromtransmitter units 121A, 121B to receiver/data processing unit 130), oralternatively, bi-directional between the two or more devices.Alternatively, the data communication link connecting the transmitterunits 121A and 121B to the receiver/data processing unit 130 may includewired cable connection such as, for example, but not limited to RS232connection, USB connection, or serial cable connection.

In an alternate embodiment, each of the transmitter units 121A and 121Bmay be individually coupled to a corresponding receiver section (forexample, separate receiver/data processing sections of the receiver/dataprocessing unit 130) such that each transmitter unit 121A and 121B areuniquely operatively coupled to the respective receiver/data processingunits. In addition, each receiver/data processing unit may be configuredto communicate with each other such that data from the transmitter units121A and 121B may be interchangeably communicated. Furthermore, whileFIG. 1 illustrates a single receiver/data processing unit 130, withinthe scope of the present invention, multiple discrete receiver/dataprocessing units may be provided, each uniquely configured tocommunicate with a corresponding one of the transmitter units 121A,121B.

Furthermore, in yet another embodiment of the present invention, thetransmitter unit 121A and transmitter unit 121B may be physicallycoupled in a single housing so as to provide a single transmittersection for the patient, which is configured to support multipletransmitter units 121A, 121B. Moreover, while two transmitter units121A, 121B are shown in FIG. 1, within the scope of the presentinvention, the continuous analyte monitoring system 100 may beconfigured to support additional and/or multiple transmitter units,multiple remote terminals, and receiver/data processing units.

Moreover, referring to FIG. 1, the analyte sensors 111A and 111B mayinclude, but are not limited to short term subcutaneous analyte sensorsor transdermal analyte sensors, for example, which are configured todetect analyte levels of a patient over a predetermined time period, andafter which, a replacement of the sensors is necessary. Moreover, in oneembodiment, the transmitter units 121A, 121B are configured to receiveanalyte related data from the corresponding analyte sensors 111A, 111B,respectively, and to transmit data to the receiver/data processing unit130 for further processing.

The transmitter units 121A, 121B may, in one embodiment, be configuredto transmit the analyte related data substantially in real time to thereceiver/data processing unit 130 after receiving it from thecorresponding analyte sensors 111A, 111B respectively. For example, thetransmitter units 121A, 121B may be configured to transmit once perminute to the receiver/data processing unit 130 based on analyte levelsdetected by the corresponding analyte sensors 111A, 111B respectively.While once per minute data transmission is described herein, within thescope of the present invention, the transmitter units 121A, 121B may beconfigured to transmit analyte related data more frequently (such as,for example, once every 30 seconds), or less frequently (for example,once every 3 minutes).

Additional analytes that may be monitored, determined or detected byanalyte sensors 111A, 111B include, for example, acetyl choline,amylase, bilirubin, cholesterol, chorionic gonadotropin, creatine kinase(e.g., CK-MB), creatine, DNA, fructosamine, glucose, glutamine, growthhormones, hormones, ketones, lactate, peroxide, prostate-specificantigen, prothrombin, RNA, thyroid stimulating hormone, and troponin.The concentration of drugs, such as, for example, antibiotics (e.g.,gentamicin, vancomycin, and the like), digitoxin, digoxin, drugs ofabuse, theophylline, and warfarin, may also be determined.

Moreover, within the scope of the present invention, transmitter units121A, 121B may be configured to directly communicate with one or more ofthe remote terminal 140 or the delivery unit 150, and in addition, thereceiver/data processing unit 130 may be integrated with one or more ofthe remote terminal 140 or the delivery unit 150. Furthermore, withinthe scope of the present invention, additional devices may be providedfor communication in the continuous analyte monitoring system 100including additional receiver/data processing unit, remote terminals(such as a physician's terminal) and/or a bedside terminal in a hospitalenvironment, for example.

In accordance with the various embodiments of the present invention, theanalyte sensors 111A, 111B may be inserted through the skin of thepatient using insertion devices having a predefined or configuredinsertion mechanism (spring loaded devices, for example) whichfacilitates the placement and positioning of the analyte sensors throughthe patient's skin, and so as to be in fluid contact with the patient'sanalytes. Alternatively, the sensors 111A, 111B may be manually deployedusing an insertion guide or needle.

As described in further detail below, the continuous calibration processin one embodiment includes deploying and calibrating a first sensor(e.g., analyte sensor 111A) at predetermined time intervals usingfingerstick calibrations, for example, at 10 hours, 12 hours, 24 hoursand 72 hours from the initial insertion of the first sensor 111A.Moreover, the first and subsequent analyte measurements may be obtainedafter the initial calibration at 10 hours when the analyte sensor hassubstantially reached a stability point. Thereafter, prior to thetermination of the first sensor life (for example, at the 120^(th) hourfor a 5 day sensor), a second analyte sensor (for example, sensor 111B)is inserted into the patient and during the period of overlap of thefirst and second analyte sensors 111A, 111B, the second analyte sensor111B is correlated with the first analyte sensor 111A values and thesecond analyte sensor 111B is calibrated in reference to the firstanalyte sensor 111A values such that the second analyte sensor 111B andany additional subsequent analyte sensors do not require the multiple(or preferably, any) fingerstick calibrations as is the case for thefirst analyte sensor 111A.

In this manner, the short term analyte sensors are overlapped for apredetermined time period to allow the output of the first and secondsensors to be correlated to detect potential transient sensitivity(e.g., ESA) in the second sensor. The detection of potential transientsensitivity in the second sensor can be achieved with substantialaccuracy since the first sensor has had a substantial time period (e.g.,several days of usage) to stabilize. Upon establishing an acceptablelevel of correlation, the calibration of the first sensor in oneembodiment is assigned or transferred to the second sensor. Morespecifically, in one embodiment, the continuous data from a previouslycalibrated first sensor is used as a set of reference values tocalibrate the second newly implanted sensor.

In this manner, in one embodiment of the present invention, asubstantially accurate calibration may be assigned to the second sensorwhile using no additional capillary blood glucose values forcalibration, and further, this approach of correlation and transfercalibration may be repeated for subsequent sensors in the continuousmonitoring system 100 such that analyte levels are continuouslymonitored without any interruption, for example, during the periodicsensor replacements in the continuous analyte monitoring system 100.

FIG. 2 is a flowchart illustrating the continuous calibration of analytesensors in the continuous analyte monitoring system in accordance withone embodiment of the present invention. Referring to FIG. 2, at step210 a first sensor 111A (FIG. 1) is deployed through the patient's skinso as to be in fluid contact with the patient's analyte and periodicallycalibrated at, for example, 10^(th) hour, 12^(th) hour, 24^(th) hour,and 72^(nd) hour. Data associated with the detected or monitored analytelevel from the first sensor 111A may be obtained for further analysissuch as insulin therapy and treatment on or after the 10^(th) hourcalibration when the first sensor has substantially reached anacceptable stabilization level.

More specifically, the transmitter unit 121A (FIG. 1) is configured inone embodiment to continuously transmit the data received from theanalyte sensor 111A to the receiver/data processing unit 130 (FIG. 1).The receiver/data processing unit 130 may be configured in oneembodiment, to display the received, substantially real time valuescorresponding to the patient's monitored analyte levels graphically,audibly, and/or a combination of visual and audio output includinggraphs, trend arrows, and level indicators associated with differentsound levels or ringtones based on the analyte levels.

Referring to FIG. 2, at step 220, a second analyte sensor 111B ispositioned at a predetermined time prior to the scheduled removal of thefirst analyte sensor 111A. In one embodiment, the predetermined timeoverlap between the insertion of the second analyte sensor 111B and theremoval of the first analyte sensor 111A from the patient may be a twoto ten hour period. Alternatively, the time overlap may be longer orshorter depending upon the sensor configuration and the preceding timeperiods are provided as examples for illustrative purposes only. In oneembodiment, the time overlap may be variable, such that first analytesensor 111A is removed when second analyte sensor 111B is determined tohave reached a point of stable operation. Thereafter, at step 230, theoutput data or signals from the first sensor 111A received fromtransmitter unit 121A is correlated with the output data or signals fromthe second sensor 111B received from the transmitter unit 121B. That is,the receiver/data processing unit 130 (FIG. 1) in one embodiment isconfigured to receive the simultaneous or substantially nearsimultaneous data transmission from a plurality of transmitter units inthe continuous analyte monitoring system 100. More specifically, in oneembodiment, the receiver/data processing unit 130 may be configured tocorrelate the data from the two sensors 111A, 111B so as to, forexample, determine that the correlation of the two data sets aresufficiently robust to determine the stability and thus acceptability ofthe second sensor 111B.

Referring again to FIG. 2, after correlating the data of the two sensors111A, 111B, at step 240, the second sensor is calibrated based on one ormore scaling factors associated with the two sensors 111A, 111B, fromwhich the sensitivity of the second sensor 111B may be determined.Thereafter, when the second sensor 111B is calibrated, the first sensor111A may be removed from the patient, and the data or signals associatedwith the patient's analyte levels from the second sensor 111B may beused by the patient for further analysis and/or treatment.

In the manner described above, in one embodiment of the presentinvention, there is provided a system and method of continuouslycalibrating implanted analyte sensors that provide accurate detection ofinitial instabilities of the implanted sensors, reduce the number ofrequired blood capillary tests for calibration, increase the calibrationaccuracy, and also, eliminate any gaps or interruptions in thecontinuous analyte data or record monitored by the continuous monitoringsystem 100.

Moreover, in a further embodiment, the receiver/data processing unit 130may be configured to prompt the patient for confirmation and also, forthe sensor calibration code when the receiver/data processing unit 130detects data or signals received from the transmitter unit 121B coupledto the second sensor 111B.

FIG. 3 is a flowchart illustrating correlation step 230 and calibrationstep 240 of the continuous calibration of analyte sensors in thecontinuous analyte monitoring system shown in FIG. 2 in accordance withone embodiment of the present invention. Referring to FIG. 3, at step310, the receiver/data processing unit 130 (FIG. 1) is configured tocompare the analyte associated data or signals from the transmitter unit121A corresponding to analyte levels detected by the first sensor 111Awith the analyte associated data or signals from the transmitter unit121B corresponding to analyte levels detected by the second sensor 111Bat each time period of the analyte monitoring.

Thereafter, at step 320, the receiver/data processing unit 130 isconfigured to determine a scaling factor for the second sensor 111Bbased on the data or signals from the first sensor More specifically, inone embodiment, the receiver/data processing unit 130 is configured toperform a predefined autocorrelation function to determine the scalingfactor for the second sensor 111B. Alternatively, in another embodiment,the data from the second sensor 111B is multiplied by a range ofpredetermined initial scaling factors to determine an average errorbetween the data from the first sensor 111A and the data from the secondsensor 111B. Based on the calculated average error, the scaling factoris determined as the one of the predetermined initial scaling factorswhich yields the smallest possible calculated average error.

In a further embodiment, the scaling factor may be determined bycalculating an average of the ratio of the two raw signals from thefirst sensor 111A and the second sensor 111B, or any other suitablemanner in which to determine a suitable scaling factor.

Referring to FIG. 3, after the scaling factor is determined at step 320,the scaling factor is applied to the data from the second sensor 111B atstep 330. More specifically, in one embodiment, the determined scalingfactor at step 320 is multiplied to the data from the second sensor 111Bat step 330. Thereafter, at step 340, a correlation level of the firstand second sensors 111A, 111B respectively, is determined by thereceiver/data processing unit 130 (FIG. 1). More specifically, at step340, the level of correlation of data from the first sensor 111A and thesecond sensor 111B are determined as a function of a predeterminedlimit, where, in the case where the level of correlation is too smallsuch that the minimum average error is too large, it is determined thatthe second sensor 111B is unstable.

In other words, referring back to FIG. 3, at step 340, the correlationlevel is determined and at step 350, it is determined whether thecorrelation level is above a predetermined threshold. As shown in theFigure, if it is determined at step 350 that the correlation level isnot above the predetermined threshold level, then the receiver/dataprocessing unit 130 returns the routine to step 340 to determine againthe correlation level of the first sensor 111A and the second sensor111B. If at step 350 it is determined that the correlation level isabove the predetermined threshold level, then the receiver/dataprocessing unit 130 determines that the second sensor 111B is relativelystable, and at step 360, the first sensor 111A calibration istransferred to the second sensor 111B.

In other words, once it is determined that the second sensor 111B isstable, then a sensitivity may be determined for the second sensor 111Bbased on the scaling factor determined at step 320 and the sensitivityof the first sensor 111A. This determination may be expressed asfollows:

S2=S1*ΣI ₂ /I ₁  (1)

-   -   where S2 represents the sensitivity of the second sensor 111B,        S_(i) represents the sensitivity of the first sensor 111A, and        ΣI₂/I₁ represents the scaling factor which correlates the data        of the first sensor 111A and the second sensor 111B.

In this manner, once the second sensor 111B is calibrated, the accuracyof data from the second sensor 111B is substantially similar to theaccuracy of the data from the first sensor 111A, where the calibrationof the second sensor 111B was performed without any capillary bloodglucose measurements by, for example, fingerstick testing using glucosemeters. By way of an example, based on a first sensor sensitivity Si at0.686 nA/mM, and with a scaling factor ΣI₂/I₁ of 0.725, the sensitivityS2 of the second sensor 111B is determined to be 0.497 nA/mM.

In the manner described above, in one embodiment of the presentinvention, there is provided a system and method of continuouslycalibrating implanted analyte sensors that provide accurate detection ofinitial instabilities of the implanted sensors, reduce the number ofrequired blood capillary tests for calibration, increase the calibrationaccuracy, and also, eliminate any gaps or interruptions in thecontinuous analyte data or record monitored by the continuous monitoringsystem 100.

Moreover, in accordance with the present invention, using the datacorrelation during the time period when the sensors overlap in time, thecalibration frequency may be reduced while increasing the calibrationaccuracy. Moreover, additional calibration information may also beobtained from the sensor calibration codes predetermined and assignedduring sensor manufacturing, and which may be used to improvecalibration accuracy without requiring additional or increased capillaryblood glucose testing.

FIG. 4 is a chart illustrating the timing of the continuous calibrationof analyte sensors in the continuous analyte monitoring system inaccordance with one embodiment of the present invention. Referring tothe Figure, each sensor is configured to be approximately a 5-daysensor, with only the first sensor (sensor 1) provided with fourdiscrete fingerstick calibrations using capillary blood glucosemeasurements. It can be further seen that each sensor overlaps in timesuch that a predetermined time period overlaps after the insertion andpositioning of a subsequent sensor, and before to the removal of theprior sensor. Moreover, calibration of sensor 2 and sensor 3 (andadditional sensors thereafter) are performed based on the continuouscalibration approach described above using the data correlation andtransfer calibration as described.

FIG. 5 is a chart illustrating the measured analyte values of a firstcalibrated analyte sensor in the continuous analyte monitoring system inaccordance with one embodiment of the present invention. Referring toFIG. 5, it can be seen that over the initial 60 or so hours of glucoselevel measurements, and based on the fingerstick calibration, thecalibrated sensitivity S_(i) of the first sensor may be determined (forexample, at 0.686 nA/mM). Thereafter, as described above, thesensitivity of the second and subsequent sensors may be determined basedon the first sensor sensitivity S_(i) and the optimal scaling factor.

FIG. 6 is a chart illustrating the measured analyte values of a secondanalyte sensor which is implanted while the calibrated first analytesensor is implanted in the continuous analyte monitoring system inaccordance with one embodiment of the present invention. Morespecifically, FIG. 6 illustrates, in an overlay manner, the calibratedsignals from the first sensor 111A and uncalibrated signals from thesecond sensor 111B received by the receiver/data processing unit 130over the time period during which the first sensor 111A is retained ininserted position, and while the second sensor 111B is introduced in thepatient. It should be noted that the signal count as shown on the Y-axismay be converted to a current signal level by a multiplication factor of11.5 picoamps/count.

FIG. 7 is a chart illustrating the measured analyte values of the secondanalyte sensor which is calibrated and correlated with the measuredvalues from the calibrated analyte sensor in accordance with oneembodiment of the present invention. More specifically, as can be seenfrom FIG. 7, in the scaling factor and the correlation of the data fromthe second sensor 111B with the calibrated data from the first sensor111A substantially aligns the two data sets over the overlap timeperiod, effectively, providing calibration to the raw data from thesecond sensor 111B based on the calibrated data from the first sensor111A.

FIG. 8 is a chart illustrating measured analyte values after the removalof the first analyte sensor, and from the calibrated second analytesensor in accordance with one embodiment of the present invention. InFIG. 8, it can be seen that the first sensor 111A is removed from thepatient and thus the receiver/data processing unit 130 (FIG. 1) nolonger receives data from the transmitter unit 121A coupled to thesensor 111A. On the other hand, the second sensor 111B is now calibratedand the data received from the second sensor 111B is received by thereceiver/data processing unit 130. In this manner, it can be seen thatthere is no interruption in the measured analyte levels even during thetransition state where the short term sensors are replaced.

Accordingly, a method of providing continuous calibration of analytesensors in one embodiment of the present invention includes calibratinga first sensor, receiving data associated with detected analyte levelsfrom the first sensor, and calibrating a second sensor with reference toone or more detected analyte levels from the first sensor.

The method in one embodiment may further include a step of calibrating athird sensor based on a second scaling factor and data associated withdetected analyte levels from the second sensor. Moreover, the step ofcalibrating the second sensor may in one embodiment, start after apredetermined time period has passed where the first sensor has been influid contact with an analyte of a patient, where the predetermined timeperiod may include at least approximately 90% or alternatively, 50% ofthe life of the first sensor.

In yet another embodiment, the method may further include the step ofdetermining a sensitivity of the first sensor.

In another aspect, the method may also include the step of receivingdata associated with detected analyte levels from the second sensor.

In accordance with still another embodiment, the step of calibrating thesecond sensor may include the steps of determining an analyte level, andcomparing the determined analyte level with the data associated with thedetected analyte level from the first sensor.

The step of calibrating the second sensor in yet another embodiment mayinclude the steps of determining a scaling factor based on substantiallysimultaneous data from the first sensor and the second sensor, applyingthe scaling factor to the data from the second sensor, determining acorrelation level of data from the first sensor and from the secondsensor.

In another aspect, the step of determining the scaling factor mayinclude the steps of comparing the substantially simultaneous data fromthe first sensor with the data from the second sensor, and determiningthe scaling factor based on a calculated scaling factor with the lowestlevel of average error between the data of the first sensor and the dataof the second sensor.

The method in yet another embodiment may include the step of comparingthe correlation level with a predetermined correlation thresholddefining an acceptable stability level of the second sensor.

The first sensor and the second sensor may be analyte sensors.

This may further include the step of removing the first sensor whileretaining the second sensor in fluid contact with the analyte of apatient.

In addition, the first sensor and the second sensor may besubcutaneously positioned under a skin of a patient, where at least aportion of the first sensor and at least a portion of the second sensorare in fluid contact with the patient's analyte.

A system for providing continuous analyte sensor calibration inaccordance with another embodiment of the present invention includes afirst sensor for subcutaneous placement in a patient, a second sensorfor subcutaneous placement in the patient after calibration of the firstsensor, where at least a portion of the first sensor and at least aportion of the second sensor are in fluid contact with the patient'sanalyte substantially simultaneously for a time period.

In one aspect, the time period may be predetermined and includesapproximately 2 hours to 10 hours.

Alternatively, in another aspect, the time period may be variable, andwhere the variable time period may be determined to be when the analytelevels measured by the first and second sensors are within a correlationrange, the correlation range being determined by a preset thresholdvalue.

The second sensor may subcutaneously placed in the patient after apredetermined time period has passed where the first sensor has been influid contact with an analyte of a patient, and where the predeterminedtime period includes at least approximately 90% or 50% of the life ofthe first sensor.

In a further embodiment, the first sensor may be operatively coupled toa first transmitter unit, and the second sensor is operatively coupledto a second transmitter unit, the first and second transmitter unitsconfigured to receive data from the corresponding first and secondsensors, respectively, for transmission over a communication link.

The first transmitter unit and the second transmitter unit may becoupled to a single transmitter housing.

The communication link may include one or more of an RF communicationlink, a Bl_(uetoot)h® communication link, an infrared communicationlink, or a cable communication link.

The system in another embodiment may include a receiver unit configuredto substantially simultaneously receive data from the first transmitterunit and the second transmitter unit.

The receiver unit may include a first receiver section operativelycoupled to the first transmitter unit, and a second receiver sectionoperatively coupled to the second transmitter unit, the second receiversection further operatively coupled to the first receiver section fordata communication.

The receiver unit may also include an infusion device.

The receiver unit may be configured to calibrate the second sensor basedon analyte levels measured by the first sensor.

The receiver unit may be configured to receive data from one or more ofthe first sensor or the second sensor at predetermined time intervalssuch that there is no interruption in the received data after the firstsensor is removed from the patient.

A method in another embodiment of the present invention may includepositioning a first sensor in fluid contact with an analyte of apatient, calibrating the first sensor, positioning a second sensor influid contact with the analyte of the patient after calibrating thefirst sensor, calibrating the second sensor based on data from the firstsensor, and removing the first sensor while retaining the second sensorin fluid contact.

The second sensor in one embodiment may be subcutaneously placed in thepatient after a predetermined time period has passed where the firstsensor has been in fluid contact with an analyte of a patient.

In one embodiment, the stability of the second sensor may be verified bycorrelation of its output with the output of the stabilized firstsensor, prior to calibration of the second sensor based on data from thefirst sensor, and thereafter removing the first sensor while retainingthe second sensor in fluid contact.

A system for determining the stability of an analyte sensor calibrationin accordance with still yet another embodiment includes a first sensorfor subcutaneous placement in a patient, and a second sensor forsubcutaneous placement in the patient after calibration of the firstsensor, where at least a portion of the first sensor and at least aportion of the second sensor are in fluid contact with the patient'sanalyte substantially simultaneously for a time period, and further,where the stability of the second sensor is determined with reference todata from the first sensor.

The time period may be predetermined and includes approximately 2 hoursto 10 hours.

Alternatively, the time period may be variable, and where the variabletime period may be determined to be when the analyte levels measured bythe first and second sensors are within a correlation range which may bedetermined by a preset threshold value.

A system for determining analyte concentrations in yet anotherembodiment includes a plurality of analyte sensors, a plurality oftransmitter units, each of the plurality of transmitter unitsoperatively coupled to a respective one of the plurality of analytesensors, a single receiver unit configured to receive and process datasubstantially simultaneously from all of the plurality of transmitterunits, where each transmitter is uniquely couple to a single analytesensor.

The receiver unit may also include a comparison unit for comparing theone or more signals from the plurality of transmitter units, and alsofor determining the stability of the plurality of sensors. In addition,the receiver unit may be further configured to determine the calibrationof the plurality of sensors based on the comparison unit.

Various other modifications and alterations in the structure and methodof operation of this invention will be apparent to those skilled in theart without departing from the scope and spirit of the invention.Although the invention has been described in connection with specificpreferred embodiments, it should be understood that the invention asclaimed should not be unduly limited to such specific embodiments. It isintended that the following claims define the scope of the presentinvention and that structures and methods within the scope of theseclaims and their equivalents be covered thereby.

What is claimed is:
 1. A receiving device for a glucose monitoringsystem, comprising: a communication unit configured to wirelesslycommunicate with a first transmitter unit, wherein the first transmitterunit is electrically and communicatively coupled to a first glucosesensor comprising a plurality of electrodes including a workingelectrode and a reference electrode, wherein the first glucose sensor ispositioned with a first portion of the first glucose sensor above auser's skin and a second portion of the first glucose sensor insertedthrough the skin and in contact with a bodily fluid of the user, whereinthe first glucose sensor is configured to detect a glucose level of thebodily fluid, wherein the first glucose sensor is configured to expireafter an amount of time corresponding to a sensor life time period haselapsed after the first glucose sensor is positioned, and a secondtransmitter unit wherein the second transmitter unit is electrically andcommunicatively coupled to a second glucose sensor comprising aplurality of electrodes including a working electrode and a referenceelectrode, wherein the second glucose sensor is positioned with a firstportion of the second glucose sensor above the user's skin and a secondportion of the second glucose sensor inserted through the skin and incontact with the bodily fluid, wherein the second glucose sensor isconfigured to detect the glucose level of the bodily fluid; one or moreprocessors operatively coupled to the communication unit; and a memoryoperatively coupled to the one or more processors for storinginstructions which, when executed by the one or more processors: receiveone or more first data signals from the first transmitter unit, whereinthe first data signals received from the first transmitter unit areassociated with one or more glucose levels of the bodily fluid detectedby the first glucose sensor; receive, while the first glucose sensor ispositioned with the second portion of the first glucose sensor insertedthrough the skin and the second glucose sensor is positioned with thesecond portion of the second glucose sensor inserted through the skin, auser input corresponding to a code; receive one or more second datasignals from the second transmitter unit, wherein the second datasignals received from the second transmitter unit are associated withone or more glucose levels of the bodily fluid detected by the secondglucose sensor, wherein the communication unit is configured towirelessly communicate with the second transmitter unit aftertermination of wireless communication with the first transmitter unit;process the second data signals to produce one or more processed datasignals; and provide the processed data signals for display.
 2. Thereceiving device of claim 1, wherein the first glucose sensor and thesecond glucose sensor are positioned prior to the expiration of thefirst glucose sensor and during an overlap time period.
 3. The receivingdevice of claim 2, wherein the overlap time period is less than 10hours.
 4. The receiving device of claim 2, wherein the overlap timeperiod is less than 10% of the sensor life time period.
 5. The receivingdevice of claim 1, wherein, during the overlap time period, the secondglucose sensor reaches a point of stable operation.
 6. The receivingdevice of claim 1, wherein the user input corresponding to the code isreceived before wireless communication with the first transmitter unitis terminated.
 7. The receiving device of claim 1, wherein the userinput corresponding to the code is received after wireless communicationwith the first transmitter unit is terminated.
 8. The receiving deviceof claim 1, wherein the communication unit is configured to wirelesslycommunicate with the first transmitter unit and the second transmitterunit substantially simultaneously.
 9. The receiving device of claim 1,wherein the code is determined during a manufacturing process of thesecond glucose sensor.
 10. The receiving device of claim 1, wherein thecode comprises a sensor code associated with the second glucose sensor.11. The received device of claim 1, wherein the code is furtherassociated with sensor calibration of the second glucose sensor.
 12. Thereceiving device of claim 1, wherein the instructions, when executed bythe one or more processors, further use the code to calibrate the seconddata signals while processing the second data signals.
 13. The receivingdevice of claim 1, wherein the communication unit is configured towirelessly communicate with the first transmitter unit and the secondtransmitter unit using a Bluetooth-enabled communication protocol. 14.The receiving device of claim 1, wherein the instructions, when executedby the one or more processors, cause display of a prompt to enter thecode.
 15. The receiving device of claim 14, wherein the prompt isdisplayed prior to termination of wireless communication between thereceiving device and the first transmitter unit.
 16. The receivingdevice of claim 14, wherein the prompt is displayed prior to thereceiving unit processing the second data signals.
 17. The receivingdevice of claim 1, wherein the second glucose sensor is calibratedwithout a fingerstick measurement.
 18. A method for monitoring glucoselevels in a bodily fluid of user with a first glucose sensor, a secondglucose sensor, and a receiving device, the method comprising:positioning the first glucose sensor with a first portion of the firstglucose sensor above a user's skin and a second portion of the firstglucose sensor inserted through the skin and in contact with the bodilyfluid of the user, wherein the first glucose sensor comprises aplurality of electrodes including a working electrode and a referenceelectrode and is configured to detect a glucose level of the bodilyfluid, wherein the first glucose sensor is electrically andcommunicatively coupled to a first transmitter unit configured towirelessly communicate with the receiver unit, wherein the first glucosesensor is configured to expire after an amount of time corresponding toa sensor life time period has elapsed after the first glucose sensor ispositioned; positioning the second glucose sensor with a first portionof the second glucose sensor above the user's skin and a second portionof the second glucose sensor inserted through the skin and in contactwith the bodily fluid of the user, wherein the second glucose sensorcomprises a plurality of electrodes including a working electrode and areference electrode and is configured to detect a glucose level of thebodily fluid, wherein the second glucose sensor is electrically andcommunicatively coupled to a second transmitter unit configured towirelessly communicate with the receiver unit; before removing the firstglucose sensor from the skin, providing, to the receiver unit, a userinput corresponding to a code, wherein the receiver unit comprises acommunication unit configured to wirelessly communicate with the firsttransmitter unit and the second transmitter unit, wherein thecommunication unit is configured to wirelessly communicate with thesecond transmitter unit after termination of wireless communication withthe first transmitter unit; and removing the first glucose sensor fromthe skin.
 19. The method of claim 18, wherein the first glucose sensorand the second glucose sensor are positioned prior to the expiration ofthe first glucose sensor and during an overlap time period.
 20. Themethod of claim 19, wherein the overlap time period is less than 10hours.
 21. The method of claim 19, wherein the overlap time period isless than 10% of the predetermined time period after the first glucosesensor is positioned.
 22. The method of claim 18, further comprisingfurther providing the user input corresponding to the code beforeexpiration of the first glucose sensor.
 23. The method of claim 18,further comprising further providing the user input corresponding to thecode in response to a prompt displayed by the receiver unit requestingthe code.
 24. The method of claim 18, further comprising furtherproviding the user input corresponding to the code before wirelesscommunication with the first transmitter unit is terminated.
 25. Themethod of claim 18, further comprising further removing the firstglucose sensor from the skin after wireless communication between thecommunication unit and the first transmitter unit is terminated.
 26. Themethod of claim 18, further comprising further removing the firstglucose sensor from the skin after the second glucose sensor reaches apoint of stable operation.
 27. The method of claim 18, wherein thesecond glucose sensor is calibrated without a fingerstick measurement.28. The method of claim 18, wherein the communication unit is configuredto wirelessly communicate with the first transmitter unit and the secondtransmitter unit substantially simultaneously.
 29. The method of claim18, wherein the code is determined during a manufacturing process of thesecond glucose sensor.
 30. The method of claim 18, wherein the code isfurther associated with sensor calibration of the second glucose sensor.